When
Where
Aaron Wilber
Professor of Psychology
Dorothy Crooker-Steves Professor of Memory
Program in Neuroscience
Florida State University
A cortico-hippocampal network for reference frame coordination and dysfunction in Alzheimer’s disease
Abstract: Navigating space and forming memories based on experience are crucial for survival, including storing memories in an allocentric (map-like) framework and coordinating them with egocentric (body-centered) actions. For example, recalling a city’s layout to choose the correct turn is thought to rely on interactions within a parietal-retrosplenial cortex-anterior thalamic-hippocampal network. Many theoretical and computational models of reference frame transformation suggest this network; however, the mechanisms and neurobiology underlying such transformations remain unclear. Deficits in spatial learning and memory occur in aging and Alzheimer’s disease (AD), and these deficits may involve the loss of a specific spatial reference frame or a loss of coordination across reference frames. Abnormal parietal-hippocampal communication is also prominent in humans with AD. Thus, understanding the neurobiological mechanisms underlying reference frame coordination and parietal-hippocampal functional interactions is critically important for establishing a complete understanding of the neural underpinnings of spatial deficits in health, aging and disease.
I begin by briefly summarizing our recent work examining hippocampal-parietal coordination for route-centered, allocentric place, and egocentric representations using a complex sequence task for rats. We found bidirectional functional hippocampal-parietal interactions, but this task does not delineate precise periods of egocentric and allocentric reference frame use. Therefore, we developed and made freely available a novel task for dissecting egocentric, allocentric reference frames, and allocentric-to-egocentric transformations. I present data validating this task and demonstrating that the parietal cortex and anterior thalamus are necessary for the transformation condition of the task. I conclude this segment by presenting work underway to flush out possible egocentric, allocentric, or transformation brain states, in part with population brain states.
Next, I describe work suggesting that impaired hippocampal-cortical interactions during sleep contribute to impaired navigation in 3xTg-AD mice, including our recent finding that early 40 Hz entrainment targeted to this circuit recovers brain function and cognition. These dysfunctional hippocampal-cortical interactions during sleep motivated work underway in my lab to examine this same brain network during wake, specifically during spatial navigation tasks that require reference frame coordination. Despite human studies indicating that this reference frame coordination may be impaired in AD, studies assessing it in rodents are almost entirely absent. Thus, I conclude by describing work beginning to fill this critical gap by assessing reference frame coordination in TgF344-AD rats, showing that egocentric impairments emerged first, followed by transformation impairments.